Defective removal of DNA cross-links in a repair-deficient mutant of Chinese hamster cells.
To further understand the relationships between DNA damage, DNA repair, and cellular end points such as survival and mutation, the repair capacity of a DNA repair-deficient mutant (strain UV-20) of Chinese hamster ovary cells was characterized in response to DNA cross-linking agents. This mutant, previously shown to be hypersensitive to killing by both ultraviolet light and the cross-linking agent mitomycin C, was also found to be extremely sensitive to cis-diamminedichloroplatinum, another DNA cross-linking agent. The efficiency of DNA cross-link removal after treatment with mitomycin C or cis-diamminedichloroplatinum was measured using the technique of alkaline elution and compared in wild-type Chinese hamster ovary cells and strain UV-20. Wild-type cells removed 80 or 95% of the cross-links within 24 hr after treatment with cis-diamminedichloroplatinum or mitomycin C, respectively. In contrast, UV-20 cells, which were equally as susceptible to cross-link damage as were wild-type cells, removed only a small proportion of the cross-links made by either agent. These results emphasize the importance of DNA repair processes in modulating the cytotoxic effects of chemicals that produce DNA cross-link damage and suggest that cross-link repair in Chinese hamster ovary cells is controlled by a pathway that also repairs damage from ultraviolet radiation.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D007700:Kinetics; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009154:Mutation; D010053:Ovary
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; D004247:DNA; D002945:Cisplatin